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Friday, January 15, 2010

Mixups Sidetrack Cancer Research

More than 100 studies utilizing cancer cells were completed using the wrong cells for the focus of the study. This may contribute to the real problem surrounding perpetuating research but never finding cancer cures.

The majority of people invloved in "races for the cures" rally have no idea where the money goes.  I think it is past time for people to demand results, not just sit passively by and think that fundraising and research organizations will meet this long over due goal.

It is also time for Big PhRMA stops pushing dangerous, unproven and ineffective drugs on mainstream medicine and often desperate patients, knowing full well their products have major problesm.

By John Gever, Senior Editor, MedPage Today
January 14, 2010

Explain to interested patients that medical research often begins with "test tube" studies of isolated cells and tissues. If they are mislabeled or contaminated, the results may send researchers off in the wrong direction and the error may not be detected until other studies are performed.

Review: Three cell lines thought to be esophageal cancer cells actually came from other tumor types, potentially misdirecting clinical trials and other studies, researchers said.

Genetic profiling revealed that the cell lines SEG-1, BIC-1, and SK-GT-5 -- believed to be esophageal adenocarcinoma cells -- were really derived from lung carcinoma, colorectal adenocarcinoma, and gastric fundus carcinoma, according to Winand N.M. Dinjens, PhD, of Erasmus University in Rotterdam, Netherlands, and colleagues.

"We have identified more than 100 scientific publications in which the contaminated cell lines . . . were used," they reported online in the Journal of the National Cancer Institute.

They pointed out that at least three ongoing research projects sponsored by the National Institutes of Health were funded on the basis of these cell lines.

Dinjens and colleagues also found two ongoing clinical trials that were based on experimental results obtained with the misidentified lines -- one testing sorafenib (Nexavar), the other evaluating an investigational telomerase inhibitor.

The authors recommended that both trials be reconsidered, as the underlying rationale is now suspect, but an editorial accompanying the report suggested that stopping the trials may not be warranted.

A total of 14 esophageal adenocarcinoma cell lines are currently in use, according to Dinjens and colleagues, and these are the foundation for nearly all experimental science in the disease, in the absence of animal models and familial cases.

It is generally recognized that many cell lines have been contaminated or mislabeled, they said.

Because the original tissues from which 13 of the 14 esophageal cancer cell lines were derived remain available, the researchers set out to authenticate the lines.

They used short tandem repeat profiling to compare genotypes of the cell lines with cells from the original tissues, supplemented by analyzing the exons and the intron-exon boundaries for the TP53 gene.

The TP53 gene is stable enough that mutations should persist through many cell divisions, and should therefore match in the cell lines and original tissues.

Dinjens and colleagues found that 10 of the 13 lines they analyzed were close genetic matches for the original tissues, despite "hundreds, perhaps thousands, of culture passages."

But for SEG-1, BIC-1, and SK-GT-5, the findings showed clear differences. Their genotypes were better matches for other tumor types.

The authors indicated that the scientist who originally derived SEG-1 and BIC-1 confirmed their results for those lines.

"Clearly, contamination occurred early during establishment of the cell lines, and all of the cultures that were distributed subsequently to different laboratories were contaminated," Dinjens and colleagues wrote.
SG-GT-5 turned out to be identical to a gastric fundus tumor line known as SG-GT-2. As with the other lines, communication with the researcher who first developed SG-GT-5 established that it must have been contaminated either at the site of origin or during early exchanges of cells with other laboratories.

"This report is a call for all scientists to authenticate their cell lines," Dinjens and colleagues concluded.

In an accompanying editorial, Robert H. Shoemaker, PhD, of the National Cancer Institute, agreed that the findings were important, but he disputed the suggestion that the two clinical trials are irretrievably compromised.

In both cases, Shoemaker indicated, there are other rationales for the therapies besides the in vitro results obtained with the disgraced cell lines.

Shoemaker also noted that the phenomenon of contaminated or mislabeled cell lines is not new.

The current study's most important impact, he wrote, "will likely be the definition of 10 esophageal adenocarcinoma tumor cell lines of proven authenticity for use in studies addressing this disease."

The study was funded from internal university sources.

No potential conflicts of interest were reported by study authors or the editorialist.

Primary source: Journal of the National Cancer Institute
Source reference: Boonstra J, et al "Verification and unmasking of widely used human esophageal adenocarcinoma cell lines" J Natl Cancer Inst 2010; DOI: 10.1093/jnci/djp499.

Additional source: Journal of the National Cancer Institute
Source reference: Shoemaker R, "Identification of Bona Fide Esophageal Adenocarcinoma Cell Lines" J Natl Cancer Inst2010; DOI: 10.1093/jnci/djp526.
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